!Project Summary This application requests state-of-the-art components essential for protein NMR and metabolic studies at 600 MHz. The UCSF NMR lab has 50 laboratories engaged in a broad array of NIH funded biomedical research. Nine major users for this application are investigating: 1- intrisically disordered proteins related to Alzheimer's disease; 2-membrane proteins implicated in neurological disorders and influenza virus infection; 3-mechanisms of transcriptional and post- transcriptional gene expression in normal and virally infected cells; and 4-metabolomics studies of tumors, their response to therapies and characterization of biomarkers. While the UCSF Biomolecular NMR lab has an high-field spectrometer operating at 800 MHz, we have relied on a Varian Inova 600 MHz spectrometer as a work-horse instrument; however, this instrument is now 19 years old, and the application of state-of-the-art methods and routine work is severely limited because of the console's obsolete and limited parts. The withdrawal of Agilent (formerly Varian) from the NMR market made finding parts for this spectrometer almost impossible. Therefore, we propose to replace the console and Cryoprobe with: a Bruker BioSpin Avance III HD console; Cryoprobe optimized for protein NMR and 13C detection of rare metabolites; a sample changer to facilitate screening of small molecule fragments for drug discovery and automated metabolomics studies. The choice of Bruker is justified by the compatibility with the current Oxford 600 MHz magnet and the lack accessories offered by other vendors. The new purchase will not only benefit the users listed on this project, but an extensive network of internal and external investigators involved in biomedical research.